Article
Multidisciplinary Sciences
Hongli Jiao, Ming-Song Lee, Athillesh Sivapatham, Ellen M. Leiferman, Wan-Ju Li
Summary: This study successfully derived iPSCs from different breeds of miniature pigs and found that YMS fibroblasts showed higher reprogramming efficiency. The study also demonstrated the differentiation potential of YMS iPSC lines with a normal pig karyotype and identified the regulation of BAF60A expression by STAT3 signaling as a determinant of pig iPSC generation efficiency.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Laura M. Pikkupeura, Raul B. Bressan, Jordi Guiu, Yun Chen, Martti Maimets, Daniela Mayer, Pawel J. Schweiger, Stine L. Hansen, Grzegorz J. Maciag, Hjalte L. Larsen, Kadi Lohmussaar, Marianne Terndrup Pedersen, Joji M. Yap Teves, Jette Bornholdt, Vladimir Benes, Albin Sandelin, Kim B. Jensen
Summary: During intestinal organogenesis, the maturation of intestinal stem cells is not fully understood. In this study, we used intestinal organoid cultures to analyze the transcriptional, chromatin accessibility, DNA methylation, and three-dimensional chromatin conformation landscapes in fetal and adult epithelial cells. We found differences in gene expression, enhancer activity, 3D organization, DNA accessibility, and methylation between the two states. We identified sustained Yes-Associated Protein (YAP) activity as a major regulator of the immature fetal state, likely coordinated by changes in extracellular matrix composition.
Article
Cell & Tissue Engineering
Tiansu Wang, Allison R. Pine, Andriana G. Kotini, Han Yuan, Lee Zamparo, Daniel T. Starczynowski, Christina Leslie, Eirini P. Papapetrou
Summary: Through the combination of induced pluripotent stem cell (iPSC) and CRISPR-Cas9 technologies, a model of clonal evolution of acute myeloid leukemia (AML) was successfully developed. This model captured distinct premalignant stages and genetic features of primary human MDS and AML, ultimately identifying dysregulation of inflammatory signaling as an early and persistent event in leukemogenesis and a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Mohamed Ameen, Laksshman Sundaram, Mengcheng Shen, Abhimanyu Banerjee, Soumya Kundu, Surag Nair, Anna Shcherbina, Mingxia Gu, Kitchener D. Wilson, Avyay Varadarajan, Nirmal Vadgama, Akshay Balsubramani, Joseph C. Wu, Jesse M. Engreitz, Kyle Farh, Ioannis Karakikes, Kevin C. Wang, Thomas Quertermous, William J. Greenleaf, Anshul Kundaje
Summary: This study defines the multi-cellular epigenomic and transcriptional landscape of cardiac cellular development using single-cell chromatin accessibility maps. The research identifies dynamic transcription factor activity signatures associated with differentiation of primary cardiac cell types, and compares regulatory landscapes of iPSC-derived cardiac cell types with their in vivo counterparts. Additionally, deep learning models are used to interpret chromatin accessibility profiles and identify TF motif lexicons. The study also reveals that de novo mutations affecting chromatin accessibility are enriched in congenital heart disease (CHD) cases and validates their functional impact on developmental cell types in vitro.
Article
Immunology
Noam Kadouri, Tal Givony, Shir Nevo, Joschka Hey, Shifra Ben Dor, Golda Damari, Bareket Dassa, Jan Dobes, Dieter Weichenhan, Marion Bahr, Michelle Paulsen, Rebecca Haffner-Krausz, Marcus A. Mall, Christoph Plass, Yael Goldfarb, Jakub Abramson
Summary: This study reveals the importance of FOXN1 in the development of thymic epithelial cells and hair follicle cells, and identifies key regulatory regions and transcription factors involved in its expression.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Pierre Sabatier, Christian M. Beusch, Amir A. Saei, Mike Aoun, Noah Moruzzi, Ana Coelho, Niels Leijten, Magnus Nordenskjold, Patrick Micke, Diana Maltseva, Alexander G. Tonevitsky, Vincent Millischer, J. Carlos Villaescusa, Sandeep Kadekar, Massimiliano Gaetani, Kamilya Altynbekova, Alexander Kel, Per-Olof Berggren, Oscar Simonson, Karl-Henrik Grinnemo, Rikard Holmdahl, Sergey Rodin, Roman A. Zubarev
Summary: The authors developed a method to simultaneously measure protein expression and thermal stability changes during cell type transitions, and applied this approach to study differences between human pluripotent stem cells and other cell types. They detected alterations of protein properties in numerous cellular pathways and components, proposing a method for maintaining pluripotency.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Jingsheng Li, Chunhong Dai, Wenyan Xie, Heyao Zhang, Xin Huang, Constantinos Chronis, Ying Ye, Wensheng Zhang
Summary: This study developed a one-step strategy to efficiently target and suppress endogenous pluripotent genes in mouse ESCs and replace their expression with AID-fused transgenes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Adi Alajem, Hava Roth, Sofia Ratgauzer, Danny Bavli, Alex Motzik, Shlomtzion Lahav, Itay Peled, Oren Ram
Summary: Enhancers play a crucial role in gene regulation by increasing the likelihood of gene transcription, and are marked by histone modifications H3K4me1 and H3K27ac. DNA methylation on enhancers has traditionally been associated with repression. This study combined histone marks and DNA methylation to show that H3K4me1-marked enhancers have higher levels of methylation compared to H3K27ac-marked enhancers during mouse embryonic stem cell differentiation, indicating cellular heterogeneity in enhancer states. The enhancers identified in this study are involved in stem cell differentiation and show variation in gene expression levels, highlighting the functional relevance of enhancer-based heterogeneity in cellular dynamics.
Article
Biochemistry & Molecular Biology
Lounis Yakhou, Anaelle Azogui, Nikhil Gupta, Julien Richard Albert, Fumihito Miura, Laure Ferry, Kosuke Yamaguchi, Sarah Battault, Pierre Therizols, Frederic Bonhomme, Elouan Bethuel, Arpita Sarkar, Maxim V. C. Greenberg, Paola B. Arimondo, Gael Cristofari, Olivier Kirsh, Takashi Ito, Pierre-Antoine Defossez
Summary: Epigenetic mechanisms play crucial roles in establishing and maintaining cellular identities in mammals. They regulate the expression of genes, transposable elements, and chromatin structures, and are essential for mammalian development. Bivalent promoters are particularly important during differentiation and development. BEND3 has been identified as a regulator of bivalent promoters, and its absence leads to genome-wide DNA methylation gains and reduced DNA hydroxymethylation, suggesting its direct and indirect roles in chromatin regulation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Zhipeng Sun, Todd G. Nystul, Guohua Zhong
Summary: In this study, the researchers used single-cell RNA sequencing, RNAi screen, and bioinformatic analysis to identify genes involved in germ cell differentiation. They discovered that a gene named eggpl is highly expressed in ovarian germline stem cells and downregulated in early daughter cells. Knockdown of eggpl resulted in defects in germ cell proliferation and differentiation. Furthermore, the downregulation of eggpl was found to link nutritional status to germ cell proliferation and differentiation. This study provides new insights into the signaling networks regulating early germ cell development and identifies eggpl as an important player in this process.
Article
Multidisciplinary Sciences
Amanda J. Collier, Adam Bendall, Charlene Fabian, Andrew A. Malcolm, Katarzyna Tilgner, Claudia Semprich, Katarzyna Wojdyla, Paola Serena Nisi, Kamal Kishore, Valar Nila Roamio Franklin, Bahar Mirshekar-Syahkal, Clive D'Santos, Kathrin Plath, Kosuke Yusa, Peter J. Rugg-Gunn
Summary: Identifying essential regulators and major impediments of human primed to naive pluripotent stem cell reprogramming through genome-wide screening, it was discovered that factors crucial for cell state change are typically repurposed with new functions rather than undergoing changes at the gene expression level. In addition, small-molecule inhibitors of reprogramming impediments were found to enhance naive cell reprogramming beyond current methods. This work not only defines principles controlling the establishment of human naive pluripotency, but also provides new insights into mechanisms destabilizing and reconfiguring cell identity during cell state transitions.
Article
Biology
Dennis May, Sangwon Yun, David G. Gonzalez, Sangbum Park, Yanbo Chen, Elizabeth Lathrop, Biao Cai, Tianchi Xin, Hongyu Zhao, Siyuan Wang, Lauren E. Gonzalez, Katie Cockburn, Valentina Greco
Summary: Stem cell differentiation involves dramatic changes in gene expression and global remodeling of chromatin architecture. In this study, a quantitative pipeline using fluorescently-tagged histones and longitudinal imaging was developed to track chromatin compaction changes in live mice. Analysis of epidermal stem cells reveals that cell-to-cell chromatin compaction heterogeneity is independent of cell cycle status and reflective of differentiation status. Furthermore, live imaging of Keratin-10 nascent RNA shows that transcription precedes global chromatin compaction changes during differentiation. These findings highlight the dynamic transcriptional states and gradual chromatin rearrangement involved in stem cell differentiation.
Article
Biochemistry & Molecular Biology
Gianluca Sigismondo, Lavinia Arseni, Nicolas Palacio-Escat, Thomas G. Hofmann, Martina Seiffert, Jeroen Krijgsveld
Summary: The DNA damage response (DDR) plays a crucial role in maintaining genome stability and its dysregulation can lead to carcinogenesis. This study focuses on the role of chromatin in regulating the DDR, including DNA, histone post-translational modifications (hPTMs), and chromatin-associated proteins. Using multi-layered proteomics, the researchers characterize the functional interactions of repair proteins, hPTM signatures, and the DNA-bound proteome during DNA double-strand break (DSB) repair. The findings provide insights into the dynamics of DDR-associated factors and highlight novel chromatin-associated proteins involved in repair pathways. Additionally, the study identifies specific hPTMs induced by DNA damage and profiles their dynamics during the DDR. The integration of various chromatin layers reveals the role of G9A-mediated histone methylation in DSB repair via homologous recombination (HR).
NUCLEIC ACIDS RESEARCH
(2023)
Review
Cell Biology
Ying Ye, Xi Chen, Wensheng Zhang
Summary: Embryonic stem cells have a unique ability to maintain and regulate the balance between self-renewal and multi-lineage cellular differentiation, largely dependent on gene expression regulations. Chromatin remodeling complexes play a crucial role in promoting chromatin structural changes that ultimately affect ESC fate choices.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Akshaya Ramakrishnan, Aikaterini Symeonidi, Patrick Hanel, Katharina T. Schmid, Maria L. Richter, Michael Schubert, Maria Colome-Tatche
Summary: This article introduces an algorithm called epiAneufinder for the identification of single-cell copy number alterations from scATAC-seq data and explores the clonal heterogeneity in cell populations.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Galya Monderer-Rothkoff, Nitzan Tal, Marina Risman, Odem Shani, Malka Nissim-Rafinia, Laura Malki-Feldman, Vera Medvedeva, Matthias Groszer, Eran Meshorer, Sagiv Shifman
Summary: Mutations in AUTS2 gene are associated with autism, intellectual disability, and microcephaly. Transition from long to short isoform of AUTS2 is crucial for regulating transcription and neuronal differentiation.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemical Research Methods
Siu Kwan Sze, Gnanasekaran JebaMercy, SoFong Cam Ngan
Summary: Deamidation is a degenerative protein modification that disrupts protein structure and function, playing a critical role in human aging and degenerative diseases. However, the study of deamidation has been limited by technical challenges in complex biological samples. New technologies, such as mixed mode electrostatic-interaction modified hydrophilic interaction liquid chromatography (emHILIC), are being developed to overcome these challenges and accurately analyze protein deamidation in complex samples.
Article
Pharmacology & Pharmacy
Karim Salhadar, Allanah Matthews, Viswanathan Raghuram, Kavee Limbutara, Chin-Rang Yang, Arnab Datta, Chung-Lin Chou, Mark A. Knepper
Summary: This passage discusses the regulation of kidney water excretion by vasopressin through the V2R receptor and the use of modern protein mass spectrometry techniques to study protein phosphorylation changes. The data generated from phosphoproteomic studies are valuable resources for understanding vasopressin signaling and signaling downstream from other G-protein-coupled receptors.
MOLECULAR PHARMACOLOGY
(2021)
Article
Cell Biology
Patrick S. L. Lim, Eran Meshorer
Summary: The article summarized the epigenetic characteristics defining the pluripotent state, discussed the current understanding of the epigenome of pluripotent stem cells, and reflected on the use of experimental systems and technology methods in this field.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2021)
Article
Cell Biology
Pablo Aurelio Gomez-Garcia, Stephanie Portillo-Ledesma, Maria Victoria Neguembor, Martina Pesaresi, Walaa Oweis, Talia Rohrlich, Stefan Wieser, Eran Meshorer, Tamar Schlick, Maria Pia Cosma, Melike Lakadamyali
Summary: The study reveals that differences in nucleosome "clutch" formation in embryonic stem cells and neural progenitor cells are associated with the structure of the Pou5f1 gene and the dynamics of core histone protein H2B. The stability and mobility of H2B vary between cell types, with implications for gene regulation and cell identity.
Article
Biochemistry & Molecular Biology
Ze Qin Lim, Qing Yong Ng, Yukei Oo, Justin Jang Hann Chu, Shi Yan Ng, Siu Kwan Sze, Sylvie Alonso
Summary: PRPH plays a crucial role in EV-A71 infection by facilitating viral entry and influencing viral genome replication. The ability of EV-A71 to exploit PRPH for successful invasion of the central nervous system represents a unique attribute, with small GTP-binding protein Rac1 potentially serving as a druggable host target to limit neuroinvasion.
Review
Pharmacology & Pharmacy
Lihe Chen, Hyun Jun Jung, Arnab Datta, Euijung Park, Brian G. Poll, Hiroaki Kikuchi, Kirby T. Leo, Yash Mehta, Spencer Lewis, Syed J. Khundmiri, Shaza Khan, Chung-Lin Chou, Viswanathan Raghuram, Chin-Rang Yang, Mark A. Knepper
Summary: Systems biology is a methodological approach that investigates biological processes by integrating and analyzing large-scale data, providing insights into the mechanisms of these processes. It has been applied to study the regulation of the water channel aquaporin-2 by the neurohypophyseal peptide hormone vasopressin, through the V2 receptor and PKA activation. This research contributes to understanding the molecular mechanisms of water balance disorders and improves the treatment of related diseases.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Neurosciences
Manju Babu, Nikhil Singh, Arnab Datta
Summary: This systematic review summarizes proteomics studies on different OGD models, discusses cell-type-specific responses to oxygen and glucose deprivation, and explores the translational potential of this approach for therapeutic target and biomarker discovery.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rafael D. Melani, Vincent R. Gerbasi, Lissa C. Anderson, Jacek W. Sikora, Timothy K. Toby, Josiah E. Hutton, David S. Butcher, Fernanda Negrao, Henrique S. Seckler, Kristina Srzentic, Luca Fornelli, Jeannie M. Camarillo, Richard D. LeDuc, Anthony J. Cesnik, Emma Lundberg, Joseph B. Greer, Ryan T. Fellers, Matthew T. Robey, Caroline J. DeHart, Eleonora Forte, Christopher L. Hendrickson, Susan E. Abbatiello, Paul M. Thomas, Andy Kokaji, Josh Levitsky, Neil L. Kelleher
Summary: By studying the proteoforms expressed from human genes in different cell types and bodily fluids, we found that proteoforms provide a better description of protein-level biology and serve as more specific indicators of cell differentiation compared to proteins. In the context of liver transplantation, we utilized the Blood Proteoform Atlas to identify cell and proteoform signatures that distinguish normal graft function from graft dysfunction.
Article
Chemistry, Multidisciplinary
Uthra Balasubramaniyan Iyer, Jung Eun Park, Siu Kwan Sze, Zbynek Bozdech, Mark Featherstone
Summary: This study provides physical evidence for the presence of the Mediator complex in Plasmodium falciparum and identifies several interaction partners that play important roles in gene expression and mRNA processing. The study also suggests a possible crosstalk between endoplasmic reticulum function and the transcriptional machinery.
Article
Biochemistry & Molecular Biology
Arnab Datta, Christopher Chen, Yong-Gui Gao, Siu Kwan Sze
Summary: This study identifies blood-based biomarkers for lacunar infarction (LACI), which can be used as a complementary prognostic tool. By analyzing medium-sized extracellular vesicles (MEVs) in the plasma, alterations in proteins related to oxygen-glucose deprivation, endo-lysosomal trafficking, glucose transport, and iron homeostasis were observed. The dataset is provided as a web-based resource for further analysis and validation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Juliane O. Viegas, Gajendra Kumar Azad, Yuan Lv, Lior Fishman, Tal Paltiel, Sundararaghavan Pattabiraman, Jung Eun Park, Daniel Kaganovich, Siu Kwan Sze, Michal Rabani, Miguel A. Esteban, Eran Meshorer
Summary: CAPRIN1 is a factor that regulates an RNA degradation pathway in embryonic stem cells, and it has significant effects on early differentiation and gene expression programs.
DEVELOPMENTAL CELL
(2022)
Review
Neurosciences
Chin-Rang Yang, Euijung Park, Lihe Chen, Arnab Datta, Chung-Lin Chou, Mark A. Knepper
Summary: The advent of modern quantitative protein mass spectrometry has revolutionized biology with 'systems biology'. These methods can identify and quantify thousands of proteins and detect protein modifications like phosphorylation. This article discusses these methods and how they can be applied to study the effects of the hormone vasopressin on the water channel aquaporin-2. The insights gained provide a detailed understanding of the molecular mechanisms involved in water balance disorders.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Physiology
Euijung Park, Chin-Rang Yang, Viswanathan Raghuram, Venkatesh Deshpande, Arnab Datta, Brian G. Poll, Kirby T. Leo, Hiroaki Kikuchi, Lihe Chen, Chung-Lin Chou, Mark A. Knepper
Summary: Vasopressin regulates renal water excretion by controlling aquaporin-2 (AQP2) through phosphorylation changes in collecting duct cells. This review identifies 51 vasopressin-regulated phosphorylation sites in 45 proteins and emphasizes the importance of these sites in AQP2 regulation. The study provides web pages listing the phosphorylation sites and functions of the targeted phosphoproteins, suggesting a central role for protein kinase A (PKA) in vasopressin signaling. Other kinases, such as ERK1/2, Camkk2, Cdk18, Erbb3, Mink1, and Src, may also be involved in vasopressin-induced phosphorylation changes. Mapping the regulated phosphoproteins to various processes offers opportunities for future studies on vasopressin-mediated control of AQP2.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Cell Biology
Jose Antonio Sanchez Milan, Maria Fernandez-Rhodes, Xue Guo, Maria Mulet, SoFong Cam Ngan, Ranjith Iyappan, Maryam Katoueezadeh, Siu Kwan Sze, Aida Serra, Xavier Gallart-Palau
Summary: This study provides a comprehensive analysis of the impact of oxidative stress and phosphorylation on the aging process. The results show that trioxidized cysteine residues accumulate in the aging proteome and interact with enzymes involved in phosphorylation signaling, altering their structures in a similar way to phosphorylated serine residues. These findings are significant for understanding the interplay between oxidative stress and phosphorylation in aging, and open new avenues for research on protein modifications in chronic diseases and aging.
